Project summary Secretions from oviducts are essential for preparing gametes for fertilization, processes conserved throughout the animal kingdom. However, molecular mechanisms underlying oviduct physiology are largely unknown. Recent studies from our lab have shown that secretory cells of spermathecae and parovaria, two types of glands in Drosophila female reproductive tract, are functionally homologous to secretory cells in mammalian oviducts and play essential roles for ovulation, sperm storage, and fertilization. With the wealth of genetic tools we developed and capability of rapid and precise genetic manipulation, we propose to utilize this novel Drosophila system to elucidate the conserved molecular mechanisms underlying secretory cell-regulated ovulation and sperm storage. Particularly, we will characterize the role of conserved transcription factors (NR5A-family nuclear receptor Hr39, GATA-family transcription factors Pannier and Serpent) in secretory cells for sperm storage and ovulation. We will also identify the downstream targets of these transcription factors in secretory cells to fulfill their roles and identify novel secretory factors for sperm storage using genetic screens. This work will provide a comprehensive understanding of the secretory cell physiology in female reproductive tract. The conserved nature of these signaling pathways will allow the knowledge gained from this study to be further validated in other insect species as well as in mammalian and human oviducts. Therefore, this work will ultimately reveal promising new drug targets for the alleviation of infertility, for novel contraceptive development, and for controlling malaria-bearing mosquito population, all of which are highly relevant to human health.